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She was monitored for signs and symptoms of adrenal insufﬁciency along with daily 0800h serum cortisol buy viagra 50 mg without prescription erectile dysfunction pump price. She had desquamation of skin in immediate postoperative period with progressive regression of features of protein catabolism buy viagra erectile dysfunction question, resolution of diabetes purchase viagra in india generic erectile dysfunction drugs online, and reduction in doses of antihypertensive drugs. Cushing’s syndrome is a disorder of chronic glucocorticoid excess and is char- acterized by features of protein catabolism along with varying signs and symp- toms. The most common cause of Cushing’s syndrome is exogenous administration of glucocorticoids. The clinical features that best discriminate Cushing’s syndrome are prototype manifestations of protein catabolism and include easy bruisibility, proximal muscle weakness, striae (especially if purplish and >1 cm wide), facial pleth- ora, and cuticular/pulp atrophy. Features like obesity, hypertension, and diabe- tes are not discriminatory as they are highly prevalent in general population. However, onset of hypertension, diabetes, or vertebral osteoporosis at a younger age should raise a suspicion of Cushing’s syndrome. The etiology of endogenous Cushing’s syndrome is summarized in the ﬁgure given below. Approximately 90% of patients with Cushing’s disease have microadenoma, while macroadenoma contributes to the rest. What are the conditions associated with hypercortisolemia in the absence of clinical features of Cushing ’ s syndrome? Pseudo-Cushing’s syndrome is a group of reversible disorders with subtle symptoms and signs of Cushing’s syndrome and hypercortisolism with anomalous response to dexamethasone suppression tests. Morbid obesity, depression, alcoholism, metabolic syndrome, poorly controlled diabetes, and polycystic ovarian disease are associated with pseudo-Cushing’s syndrome. Resolution of the underlying disorder leads to amelioration of pseudo-Cushing’s syndrome. Obesity is a pseudo-Cushing’s state and is associated with loss of circadian rhythm of cortisol, normal total serum cortisol, mildly increased urinary free cortisol, and variability in response to overnight dexamethasone suppression test. Obesity is associated with increased cortisol turnover, with augmented synthesis as well as clearance of cortisol, resulting in a normal circulating level of cortisol. The augmented clear- ance of cortisol is due to enhanced A-ring reduction of cortisol leading to increased urinary excretion. Cyclical Cushing’s syndrome is characterized by periods of waxing and wan- ing symptoms and signs of hypercortisolemia and anomalous results of corti- sol dynamic tests. It is biochemically deﬁned as presence of three peaks and two troughs of cortisol secretion over a period of time (usually weeks to months). These patients require frequent monitoring with urine free cortisol or late-night salivary cortisol to establish the diagnosis, as cycle length varies from days to months. Spot urine cortisol to creatinine ratio and measurement of scalp hair cortisol may also be useful. Cyclical Cushing’s syndrome can occur with pituitary (54%), ectopic (26%), or even with adrenal Cushing’s (11%). The mechanism of cyclicity are elusive; however, periodic hormono- genesis is a commonly purported mechanism; periodicity in hormone biosyn- thesis may be due to recurrent hemorrhage in the tumor or early programmed tumoral cell death. Subclinical Cushing’s syndrome is characterized by lack of speciﬁc symptoms and signs of Cushing’s syndrome, but with evidence of autonomous glucocor- ticoid secretion. However, majority of these patients have obesity, hyperten- sion, and type 2 diabetes. Causes of weight gain in a patient with Cushing’s syndrome are increased appetite, enhanced adipogenesis, ﬂuid retention, and decreased physical activity. Increased appetite is because of stimulatory effect of cortisol on feeding center through aug- mented adenosine monophosphate kinase activity, insulin resistance, decreased corticotrophin-releasing hormone, and increased neuropeptide Y. Enhanced adipo- genesis is attributed to cortisol-mediated diversion of primitive mesenchymal stem cells to adipocytes and increased activity of lipoprotein lipase and glycerol- 3-phosphate dehydrogenase. Fluid retention also contributes to weight gain and is due to action of excess cortisol on mineralocorticoid receptor (speciﬁcity spill- over). Decreased physical activity resulting from proximal muscle weakness or neuropsychiatric manifestations is also a cause of weight gain. Nearly 45% of patients with Cushing’s syndrome have central obesity as against 55% with generalized obesity. However, children with Cushing’s syn- drome usually have generalized obesity, probably due to lesser omental fat. Weight gain is a hallmark feature of Cushing’s syndrome; however, some patients may present with weight loss. The causes include adrenocortical carci- noma, ectopic Cushing’s syndrome, uncontrolled diabetes, concurrent infec- tions like tuberculosis, and endogenous depression. Headache in patients with Cushing’s syndrome can be due to adenoma per se, sinusitis, cor- tical vein thrombosis, benign intracranial hypertension, and glaucoma. Striae are one of the classical features of Cushing’s syndrome and are present in 60–70% of patients. Striae in Cushing’s syndrome are violaceous-purple, dehis- cent, >1 cm wide and are commonly present over abdomen, thighs, buttocks, arms, and inframammary region. Wide and purplish striae are due to venular dila- tation and thinned out dermis, which in turn occurs as a result of loss of perivas- cular collagen support and dermal collagen breakdown, respectively. Striae may be absent in patients with childhood Cushing’s syndrome, adrenocortical carci- noma, ectopic Cushing’s syndrome, and hypercortisolemia associated with androgen excess. Causes of striae in the absence of Cushing’s syndrome include rapid weight gain during puberty, pregnancy, and pseudo-Cushing’s states. Cutaneous manifestations of Cushing’s syndrome are bruise, striae, plethora, cutic- ular atrophy (“cigarette paper” appearance – Liddle’s sign), and fungal infections. Bruise, striae, and plethora are due to loss of dermal collagen, while cuticular atro- phy is a result of atrophy of stratum corneum. Rarely, purpura can be associated with Cushing’s syndrome due to qualitative abnormalities in platelet function. Proximal myopathy in patients with Cushing’s syndrome is due to decreased muscle protein synthesis, increased muscle protein catabolism, and myocyte apoptosis. Concurrent hypokale- mia, hypophosphatemia, hypomagnesemia, vitamin D deﬁciency, and hypogo- nadism further contribute to muscle weakness in patients with Cushing’s syndrome. Why do some patients with Cushing ’ s syndrome lack features of protein catabolism? The features of protein catabolism, also called as speciﬁc features, are present in 60–70% of patients with Cushing’s syndrome. However, these features may not be present in patients with mild Cushing’s syndrome, cyclical Cushing’s syndrome, childhood Cushing’s syndrome, and hypercortisolemia associated with androgen excess. Patients with adrenocortical carcinoma and ectopic Cushing’s syndrome may lack features of protein catabolism due to short lag time between onset of hypercortisolemia and diagnosis. Plethora is considered as a speciﬁc sign of Cushing‘s syndrome and is due to dermal collagen breakdown and increased erythropoiesis because of hypercortisolemia. Hyperprolactinemia seen in 20–30% of patients may also contribute to increased adrenal androgen production. Further, patients with Cushing’s syndrome may also have increased ﬁne hair (vellus hair), especially on the forehead, back, and extremities due to a direct effect of cortisol on pilosebaceous units. What are the causes of menstrual irregularities in patients with Cushing ’ s syndrome?

Many observational studies demonstrated an increased risk of cancer with the use of insulin glargine in patients with diabetes 100mg viagra amex erectile dysfunction va benefits. Insulin therapy is associated with weight gain as it promotes calorie retention (reduces glucosuria) viagra 25 mg discount erectile dysfunction causes anxiety, adipogenesis discount viagra 50mg line erectile dysfunction pumps review, and sodium and water retention. However, insulin detemir is weight neutral possibly because of its direct effect on satiety center or a preferential action at hepatocytes than adipocytes. Insulin detemir is a long-acting insulin analogue with peak effects at 6–8 h and duration of action lasting 8–24 h. It differs from human insulin that amino acid at the 30th position is removed and a 14-carbon aliphatic fatty acid is added at the 29th position of B-chain of insulin. This modiﬁcation increases the binding with albumin in circulation and prolongs its duration of action. In addition, minimal intra- and inter individual variability in absorption kinetics, absence of weight gain and low risk of hypoglycemia are other distinctive features of insu- lin detemir. Detemir has to be administered twice daily and ideally should not be mixed with other insulins. Degludec a long-acting insulin analogue with deletion of last amino acid from the B-chain and addition of hexadecanedioic fatty acid at 29th position. However, it differs from glargine in that it has ultra long duration of action of nearly 40 h, is truly “peakless,” has a neutral pH, ﬂexibility of administration during anytime of the day between 8 and 40 h, and can be mixed with other insulins. Although the overall risk of nocturnal hypoglycemia is lesser with insulin degludec as compared to insulin glargine, the efﬁcacy in terms of HbA1c reduction is similar. In addition, some studies suggest a relative increase in cardiovascular events with the use of degludec as compared to glargine. This was attributed to hyperinsulinemia due to degludec rather than intensive glycemic control. The modiﬁcation of an insulin molecule with deletion of last amino acid from B-chain and addition of hexadecanedioic fatty acid at 29th position creates dihexamers in the presence of phenol and zinc. When injected, phenol dif- fuses away, and this dihexamer is reorganized to multihexamer which pro- longs the resident time of insulin in subcutaneous tissue. Further, with gradual diffusion of zinc, these multihexamers slowly dissociate into readily absorb- able monomers. An ideal basal insulin should be able to provide a peakless and stable insulin levels for at least 24 hours, with minimal intra- and inter-individual variability, and minimal/no risk of hypoglycemia, weight gain and mitogenic potential. Premixed insulin consists of short-acting and intermediate-acting insulin in a ﬁxed ratio, which reduces the number of injections and increases patient’s convenience. Premixed insulin therapy is less complex than basal-bolus regi- men and provides both basal and pre-prandial insulin as a single injection. It is useful in patients with both fasting and post-prandial hyperglycemia, par- ticularly in those with some residual endogenous β-cell reserve. Premixed insulin analogues may be better than con- ventional premixed insulin for postprandial glucose control with reduced risk of hypoglycemia. Monnier’s hypothesis dissects the contribution of fasting and postprandial hyperglycemia at different levels of HbA1C. Both fasting 17 Type 2 Diabetes Mellitus 415 and post-prandial hyperglycemia contributes equally to the glycemic burden in those with HbA1C between 7. What should be targeted ﬁrst in a patient with diabetes who have both fast- ing and postprandial hyperglycemia? In addition, normalization of fast- ing plasma glucose also results in reduction of postprandial hyperglycemia as a “carryover” effect. In case of failure to control post-prandial hyperglycemia despite normalization of fasting plasma glucose, additional therapies are required to control post-prandial hyperglycemia. If post-prandial hyperglyce- mia is targeted ﬁrst in patients with both fasting and post-prandial hyperglyce- mia, subsequent addition of therapy aimed to target fasting hyperglycemia may result in increased risk of post-prandial hypoglycemia. However, further increase in doses of sulfonylurea (glimepiride >4mg/day) or metformin (>2000 mg/day) has only modest effects on glycemia. Pioglitazone may be an option; however it may not help to achieve target HbA1c in this individual. In clinical practice, basal insulin is added 416 17 Type 2 Diabetes Mellitus either in second tier or third tier to control fasting hyperglycemia, especially if HbA1c is >8. Self-monitoring of blood glucose is an integral part of diabetes management and allows the participation of patient in diabetes care, helps to guide treatment decisions and response to therapy. In the index patient, a detailed evaluation should be performed to assess hemo- dynamic stability, sensorium, hydration status and complications of diabetes. Biochemical evaluation include blood glucose, renal function test, electrolytes, serum ketones, and arterial blood gas analysis. If the patient who is hemody- namically stable and is accepting orally, basal-bolus insulin regimen should be initiated, whereas patient who have hypotension/altered sensorium/ recurrent vomiting should be managed with insulin infusion. A good glycemic control helps in early recovery, and the targets of blood glucose in a non-critically ill patient are pre-meal values <140 mg/dl and random blood glucose <180 mg/dl. Use of sliding scale regimen with short-acting insulin alone should be discour- aged as this regimen is invariably associated with marked swings in blood glu- cose proﬁle. Insulin is the preferred therapy for the management of critically ill patients with hyperglycemia. Although good glycemic control is important for early recov- ery, critically ill patients are at a higher risk of hypoglycemia when insulin therapy is initiated. Therefore, the recommended blood glucose target in this population is 140–180mg/dl. This can be accomplished by administration of intravenous insulin therapy in patients who are not allowed orally/not accepting orally. Addition of basal insulin (subcutaneous) to intravenous insulin regimen minimizes the swings in blood glucose, smoothens glycemic control and reduces the risk of hypokalemia. In patients who are on naso-gastric feed, hyperglycemia can be managed with basal-bolus regimen, preferably compris- ing of insulin analogues. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic con- trol. Microvascular complications of diabetes include retinopathy, nephropathy, and neuropathy. These complications occur due to involvement of vessels which are <10 μm in size, hence the name “microvascular. Microvascular complications are a function of duration of diabetes, and the risk is continuous at all levels of hyperglycemia. These com- plications do occur even in subjects with prediabetes, although at a much lower frequency (3–10%), as opposed to 50–90% of patients with diabetes. Chronic hyperglycemia results in initiation of a cascade of events that eventu- ally leads to microvascular damage. Advanced glycosylation end products are the result of nonenzymatic glycosyl- ation of glucose with amino group of intra- and extracellular proteins or lipids.

This is exemplified by the opiate analgesics where the concentration versus effect curve for analgesic effects and that for the respiratory depressant effects are different and modulated by two distinct receptors discount 25mg viagra with mastercard erectile dysfunction is often associated with quizlet. A clinical example of this later situation is seen with the rapid onset of respiratory depression after dose escalation of opiates as tolerance develops to the analgesic effects cheap generic viagra uk erectile dysfunction causes weight. With few exceptions buy cheapest viagra and viagra vegetable causes erectile dysfunction, it is rarely possible to measure drug concentrations at or near the receptor given that their primary location is in the tissue biophase, not in the plasma. In most instances, a change in a given surrogate measurement is examined in association with the plasma drug concentration versus time curve to assess pharmacodynamic properties. For drugs whose pharmacokinetic properties are best described by first-order (as opposed to zero- or mixed-order) processes, a semi-logarithmic plot of plasma drug concentration versus time data for an agent given by an extravascular route of administration (e. After the time where maximal plasma concentrations (Cmax) are observed, the plasma concentration decreases as metabolism and elimination become rate limiting; the terminal portion of this segment of the plasma concentration versus time curve being representative of drug elimination from the body. By being able to characterize the pharmacokinetics of a specific drug, the clinician can use the data to individualize drug–dosing regimens so as to compensate for factors that can influence pharmacokinetics (e. For drugs where a therapeutic plasma concentration range and/or “target” systemic exposure (i. When linked with information regarding the pharmacodynamic behavior of a drug and the status of the patient (e. Panel B illustrates developmental differences in body composition which can influence the apparent volume of distribution for drugs. Panel C illustrates the ontogeny of factors pertaining to gastrointestinal physiologic function, one or more of which can influence either the rate and/or extent of drug absorption. Panel D illustrates the acquisition of renal function (both glomerular filtration rate and active tubular secretory capacity reflected by para-aminohippuric acid clearance, a validated biomarker) during development. Panel E illustrates the impact of development on aspects of the integumentary system which collectively, can modulate the systemic absorption of drugs applied to the skin. Developmental pharmacology—drug disposition, action and therapy in infants and children. Accumulated information supports that many of these changes are indeed predictable (4) and consequently, they can be used to inform the design of pediatric clinical trials through the use of modeling and simulation and also, to clinically individualize drug treatment for a given patient based on known or expected pharmacokinetic behavior of a given drug (5). An example of therapeutic utility of pharmacokinetic-based optimization of drug treatment has been recently illustrated in the provision of antiretroviral therapy in children (6). For the clinical application of such data, it is important for the clinician to have a conceptual understanding of how development influences both drug disposition and effect. In the following paragraphs, we provide a summary of developmental pharmacokinetics, much of which has been excerpted (with permission) from previous works (1,7,8) published by one of the co-authors (G. These publications can be referred to for reference to citations in the primary literature upon which the following summaries are based. Drug Absorption Absorption of drugs administered by extravascular routes occurs largely via passive diffusion. At certain anatomical sites where drug transport proteins are expressed, absorption can occur via active transport or facilitated diffusion. In addition to physiologic changes that occur during development, the concomitant presence of certain disease states (e. A summary of important factors that can influence drug absorption in neonates, infants, and children is provided in Table 82. Oral Absorption As is the case in adults, the majority of therapeutic drugs administered in the outpatient setting are given by the oral route. During development, maturational changes of gastric, intestinal, and biliary tract function (Fig. Given that most orally administered drugs have the physicochemical property of being either a weak acid or weak base, pH within the gastrointestinal tract can influence the amount of potentially absorbable drug (i. Gastric pH changes significantly throughout development with the highest values occurring during the neonatal period. In the fully mature neonate, the gastric pH ranges from 6 to 8 at birth and drops to 2 to 3 within a few hours of birth. However, after the first 24 hours of postnatal life, the gastric pH increases due to the immaturity of the parietal cells and gradually reaches expected adult values (e. As a result of these developmental differences, the bioavailability of acid-labile drugs (e. During development, one of the most important physiologic changes capable of altering the rate of drug absorption resides with gastrointestinal motility. By 6 to 8 months of age, gastrointestinal transit times may be shorter than those observed for older children and adults; a situation which can significantly influence both the rate and extent of bioavailability of drugs with limited water solubility (e. Finally, immature biliary function in neonates and young infants in the first few months of life has the potential for reducing the extent of oral bioavailability of lipophilic drugs which are dependent upon bile acids for their solubility in the small intestine (e. Developmental differences in the activity of intestinal drug-metabolizing enzymes (e. The clinical consequence of this observation of diminished expression in neonates and infants would be reduced presystemic clearance of substrates for these drug- metabolizing enzymes and higher circulating concentrations of the active compound in plasma (e. Conversely, if the medication is administered as a prodrug which is activated by these enzymes, we would expect reduced concentrations of the active compound in the plasma (e. While the patterns of ontogeny for these enzymes and transporters are not concordant, the majority appear to have adult expression within the first 6 to 12 months of postnatal life at which time, the influence of development on their activity as a determinant of bioavailability would be expected to be minimal (9,10). Extravascular Drug Absorption As is the case with oral drug absorption, development can influence the bioavailability of drugs administered by other extravascular routes (e. In the neonate, muscular blood flow is reduced in the first few days of life, as is the relative efficiency of muscular contractions. Furthermore, neonates and young infants have greatly reduced muscle mass (compared to older infants and children) an increased percentage of water per unit of muscle mass. Collectively, these developmental changes can produce variable and delayed rates of absorption of drugs given by the intramuscular route. In contrast, mucosal (rectal and buccal) and dermal permeability in the neonate and young infant is increased and thus, may result in enhanced absorption by these routes. In the case of transdermal drug absorption, a more highly perfused and hydrated stratum corneum (Fig. In addition, the ratio of body surface area to body weight is greater in infants and children as compared to adults. Collectively, these developmental differences may predispose infants and young children in the first 8 to 12 months of life to increased exposure and risk for toxicity for drugs/chemicals placed on the skin (e. Normal developmental differences in drug absorption from most all extravascular routes of administration can influence the dose–plasma concentration relationship in a manner sufficient to alter pharmacodynamics. Disease states that affect the integrity of the physiologic barriers that drugs given by extravascular routes must traverse prior to their translocation to the vascular space must be considered, as they can influence both the rate and extent of drug absorption. Finally, with regard to extravascular drug administration, it must be recognized that the onset of drug effect is directly dependent upon the route of administration. For example, the onset of effect for most drugs given intravenously in most cases, virtually instantaneous.

An autoimmune T-cell–mediated process in those with a genetic susceptibility and influenced by environmental factors is suspected (69 buy viagra discount erectile dysfunction treatment in kuala lumpur,81 order 100mg viagra mastercard erectile dysfunction yahoo,109 best purchase viagra erectile dysfunction without pills,122,123,126,127,136,137,139). Over time, there is a reactive fibrosis in the intima and neovascularization at the intimal–medial junction. Vascular pathology evolves to fibrosis and thickening in all layers, which effectively narrows or obliterates the vessel lumens (122,123,126,127,129,130). Dilation and aneurysms develop when severe or rapid inflammation leads to destruction of the elastic media and smooth muscle cells with release of matrix metalloproteinases and other oxidants (28,140). However, these phases may not be so readily distinguishable in an individual patient. The active phase may spontaneously remit after 3 months, or progress insidiously for months to years (127,129). As well, inflammatory and occlusive phases can coexist in different segments of the same vessel (28,142,143). The reported incidence of aneurysms in pediatrics varies widely, from 19% to 65% (147). The abdominal aorta is a frequent site of aneurysm development, but has been reported in the subclavians and thoracic aorta as well (81,139,145,146,148,149,150). Aortitis can result in fibrous leaflet thickening and leaflet retraction or even separation of leaflet attachments to ascending aorta (32,153,154). Aortic root or ascending aorta dilation can affect leaflet coaptation detrimentally. Type I: Stenosis or occlusion of the ostia or proximal coronary (usually left main). This is the most commonly detected coronary abnormality, and reflects extension of aortitis with inflammation of intima and contraction of fibrotic media, adventitia from ascending aorta. High afterload from large vessel stenosis such as mid-aortic syndrome may also contribute to ventricular dysfunction (135,160). Peripheral pulmonary arterial involvement is commonly seen angiographically but is typically mild. Typically, pulmonary artery involvement coincides with extensive aortic disease as well (163,164). Arrhythmias: ventricular arrhythmias and complete heart block have been reported (129,165,166). Presentation Presentation is highly variable in pediatrics, from no symptoms to severe neurologic symptoms to congestive heart failure (28,168). Weight loss, fatigue, anorexia, fever, and dyspnea have been reported as most common presenting symptoms in children (122,123,126). However, children may also present with symptoms suggestive of vascular insufficiency from stenosis or occlusion such as paresthesias, claudication, abdominal pain, headache, dizziness, palpitations, chest pain, and syncope (122,123,126,129,130). Fundoscopic changes secondary to common carotid or vertebral stenosis are less common in children than adults (129,144). Biomarker pentraxin-3, a protein produced in endothelial and other cells in response to inflammatory signals, has demonstrated better sensitivity and specificity than other biomarkers for monitoring active disease, particularly after steroid treatment (2,32,34,69,72,109,120,142,144,171). Imaging is vital to assess luminal and mural changes, monitoring disease activity over time, and response to treatment (31,172,173,174). In an individual patient, a variety of imaging modalities are likely to be employed depending on the clinical need while balancing risks of anesthesia and radiation. The “Macaroni phenomena” is described as a diffuse, homogeneous, hyperechoic circumferential intima–media wall thickening with narrowed lumen. Because the diagnosis is rare and the acute phase symptoms are so nonspecific, diagnosis is often delayed in the pediatric population, four times longer than in adults. Cyclophosphamides, anakinra, or mycophenolate has been utilized in challenging cases (79,87). As well, patients on chronic steroids with obesity, hypertension, and lipid abnormalities are at higher risk for arterial ischemia (63,65,102,144). Hypertension can be difficult to manage and hypertensive crisis can occur, requiring intensive care and intravenous medications and prompting need for urgent vessel intervention. Intervention: if the patient develops symptoms or signs of ischemia or concern for potential end-organ damage, revascularization procedures such as angioplasty, stenting, or vascular bypass grafts may be utilized. When possible, intervention should be avoided during the active phase of the disease to decrease morbidity and mortality, improve efficacy, and achieve longer-lasting results (2,32,34,66,67,68,99,103,104,105,106,107,108,109,169,170,171,172,173,174). Saphenous vein grafts are typically employed as involvement or recurrence of disease in the innominate or subclavian arteries preclude use of the internal mammary arteries. Surgery may be needed to address combinations of severe dilation in one vessel and stenosis or occlusion in nearby vessels. Replacement of the entire ascending aorta and aortic arch and descending aorta has been described (69,110). Homograft replacement of the aortic valve and root and Ross procedures (pulmonary autograft) have also been described in pediatric Takayasu case reports (40,41,42,43,75,77,78,80,82,113,114,151,153,176,177). Coronary artery reconstruction and patch angioplasty of stenotic coronary ostia may also be necessary (28,68,84,109,115,116,117,118,119,166,174). Several composite disease activity scores have been developed, and recently applied to children (27,28,29,86,141). Sustained remission was obtained in 79% at 1 year, but dropped to 29% by 5 years (93,124,141). However, disease modifying and biologic medicines appear to be improving outcomes. In a recent Indian cohort of 40 patients under the age of 16 years, 90% survival was noted at 5 years with management in 85% of patients with steroids and immunosuppression with mycophenolate mofetil, azathioprine, or methotrexate. Characteristic features include cutaneous manifestations (heliotrope rash, Gottron papules/rash), symmetrical proximal muscle weakness, and evidence of immune-mediated vasculopathy (periungual capillary changes with telangiectasia and dropouts). Clinical characteristics include proximal and distal muscle weakness, higher muscle enzymes, and more frequent cardiac events (102,127,184). Those with abnormal strain had higher scores of long-term organ damage (myositis damage index) as well as more early disease activity in the skin (28,58,113,122,132,133,194). Multisystem involvement can include mucocutaneous, articular, neurologic, urogenital, vascular, intestinal, and pulmonary manifestations (28,43,197,198). The prevailing hypothesis has been that an autoimmune response is induced in genetically predisposed individuals by a viral, bacterial, or environmental agent and/or an autoantigen, and the autoimmune response triggers vasculitis (114,134,197). Morbidity and mortality is increased in those with cardiac involvement (27,28,29,135,198). Treatment may include optimization of immunosuppression, colchicine, pericardiocentesis, and/or pericardiectomy, depending upon the clinical scenario and response to therapy (3,27,29,31,32,199,202,203,204,205,206). Vasculitis Vasculitis with resultant vessel dilation may involve any vascular bed, including pulmonary vessels, coronaries, and great arteries though it is rare in pediatrics.